Cardiac Electrophysiology in Duchenne Muscular Dystrophy: From Basic Science to Clinical Expression

Cardiac Electrophysiology in Duchenne Muscular Dystrophy. Duchenne muscular dystrophy is an X-linked recessive neuromuscular disorder that involves striated muscle fibers (skeletal, cardiac), smooth muscle Fibers (vasculature), and nervous system (neurons of central brain and cortex). The Duchenne dystrophy gene has been identified on the Xp21 locus of the short arm of the X chromosome. Dystrophin, the protein product of the gene, is present on and limited to myogenic cells in every tissue tested except the central nervous system, and is absent or nearly so in Duchenne dystrophy. However, the function of dystrophin and the pathogenesis of Duchenne dystrophy remain unclear. There is convincing morphological (gross, histologic, ultrastructural) and metabolic evidence (positron emission tomography) that myocardial involvement is found initially in the posterobasal left ventricular wall (cardiac phenotype). This regional localization of myocardial dystrophy is believed to account for the distinctive 12-lead scalar electrocardiogram (ECG). Abnormalities of cardiac rhythm and conduction have been reported in Duchenne muscular dystrophy, but the pathogenesis of the electrophysiologic disturbances has not been established. Two variables are relevant to cardiac electrophysiologic involvement in Duchenne dystrophy: (1) the small vessel coronary arteriopathy (medial hypertrophy, luminal narrowing); and (2) abnormalities that might originate in the specialized cardiac tissues. The role of the coronary arteriopathy is presently speculative, and it is not currently known whether dystrophin is normally present on the cell membrane of normal cardiac specialized tissues, and if so, whether those tissues are dystrophin deficient in Duchenne dystrophy. Animal models (mouse, cat, dog) have shed light on the pathogenesis of skeletal muscle and myocardial involvement, less so on involvement of cardiac specialized tissues. The determinants of calcium homeostasis in dystrophin-deficient myogenic cells (skeletal or cardiac) is unclear, and the relationship between dystrophin deficiency, calcium homeostasis, cellular response and phenotypic expression in skeletal muscle and myocardium is imperfectly understood. The purpose of this report is to bring together current genetic, molecular biological, biochemical, histopathological, and clinical information from human Duchenne dystrophy and from animal models bearing on the electrophysiologic expressions of the neuromuscular disease. (J Cardiovasc Electrophysiol, Vol. 3, pp. 394–409, August 1992)     

Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori

Abstract Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence. The most commonly used regimen for H. pylori infection is triple antimicrobial therapy for 1-2 weeks. This treatment is associated with frequent side effects and hence unsatisfactory compliance. As in vitro data showed that H. pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H. pylori infection were studied. Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg. The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H. pylori. Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen. In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H. pylori infection in patients with endoscopically confirmed duodenal ulcers. The patients were also treated with 4 weeks of omeprazole. Clearance of H. pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients. However, when the biopsies were repeated at 8 weeks, recurrence of H. pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication. It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H. pylori infection.     

Anatomy of the Coronary Sinus and Epicardial Coronary Venous System in 620 Hearts: An Electrophysiology Perspective

Anatomy of the Coronary Venous System . Introduction: Cannulation of the coronary sinus (CS) is a prerequisite for left ventricular (LV) pacing and certain ablation procedures. The detailed regional anatomy for the coronary veins and potential anatomic causes for difficulty with these procedures has not been established. Methods and Results: Therefore, we performed macroscopic measurements in 620 autopsied hearts (mean age 60 ± 23 years, 44% female). The CS was preserved for analysis in 96%. Sixty‐three percent had a Thebesian valve that covered the posterior aspect of the CS ostium with extension to the superior (50%) and inferior aspects (18%) and was obstructive with fenestrations in 3 specimens. Partial or near occlusive valves were present occasionally at the ostium of the great cardiac vein (Vieussens; 8%) and middle cardiac vein (5%). Ninety‐three percent had left atrial branches, and 41% had at least one branch with lumen > 3 French. For CRT lead placement, the mid‐lateral LV was accessible from the middle cardiac vein (20%), the left posterior vein (92%) or the anterior interventricular vein (86%). Among specimens where the left phrenic nerve was preserved it crossed the LV mid‐lateral wall in 45%. Conclusions: Epicardial coronary vein anatomy is variable, and the mid‐lateral LV wall can potentially be accessed through various tributaries of the epicardial veins. The orientation of the Thebesian valve favors cannulation of the CS from an anterior (ventricular) and inferior approach. Anterobasal, mid‐lateral, and inferior apical LV coronary veins lie in proximity to the course of the phrenic nerve. (J Cardiovasc Electrophysiol, Vol. 24, pp. 1‐6, January 2013)     

A Life‐Threatening Flecainide Overdose Treated with Intravenous Fat Emulsion

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life‐threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life‐threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE should be considered as a novel adjunctive therapy in patients with life‐threatening toxicity following flecainide overdose.